Translational Medical Research Commons^™

Barriers And Facilitators To Implementing Simulation-Based Translational Research: A Qualitative Study, Lisa Ann Paganotti

Doctor of Philosophy in Translational Health Sciences Dissertations

Translational simulation research has the potential to inform the way simulation is used to impact patient care and patient outcomes. Understanding how to approach translational simulation and the barriers and facilitators that can be used throughout the process can inform novice simulation and translational researchers. This qualitative dissertation sought to answer the following research questions: How do simulation experts describe the barriers and facilitators to implementing translational simulation programs? How do simulation experts describe their various approaches to implementing translational simulation programs? What recommendations do simulation experts describe for overcoming barriers to implementing translational simulation programs? The key findings include …

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Clinical and Translational Science Faculty Publications

Background: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer’s disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

Methods: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

Micro-Computed Tomographic Analysis Of The Shaping Ability Of Xp-Endo Shaper In Oval-Shaped Distal Root Canals Of Mandibular Molars, Ane Poly, Wei-Ju Louis Tseng, Fernando Marques, Frank Carsten Setzer, Bekir Karabucak

Center for Translational Medicine Faculty Papers

Objective: To compare the shaping ability of the XP-endo Shaper (XPS) system to the ProTaper Next (PTN) system in oval-shaped distal root canals.

Methods: From 12 mandibular molars, distal roots with moderately curved single oval canals were randomly assorted to be instrumented with XPS (experimental group) or PTN (control group) and then scanned using micro-computed tomography [Scan 1]. The root canals of the XPS samples were prepared following the manufacturer's instructions using 15 insertions (XPS15) and rescanned [Scan 2]. An additional 10 insertions to the working length were applied, totalling 25 insertions (XPS25), and the roots were rescanned again [Scan …

Activation Of Crtc2/Creb1 In Skeletal Muscle Enhances Weight Loss During Intermittent Fasting, Nelson E Bruno, Jerome C Nwachukwu, David C Hughes, Sathish Srinivasan, Richard Hawkins, David Sturgill, Gordon L Hager, Stephen Hurst, Shey-Shing Sheu, Sue C Bodine, Michael D Conkright, Kendall W Nettles

Department of Medicine Faculty Papers

The Creb-Regulated Transcriptional Coactivator (Crtc) family of transcriptional coregulators drive Creb1-mediated transcription effects on metabolism in many tissues, but the in vivo effects of Crtc2/Creb1 transcription on skeletal muscle metabolism are not known. Skeletal muscle-specific overexpression of Crtc2 (Crtc2 mice) induced greater mitochondrial activity, metabolic flux capacity for both carbohydrates and fats, improved glucose tolerance and insulin sensitivity, and increased oxidative capacity, supported by upregulation of key metabolic genes. Crtc2 overexpression led to greater weight loss during alternate day fasting (ADF), selective loss of fat rather than lean mass, maintenance of higher energy expenditure during the fast and reduced binge-eating …

Ogr1-Dependent Regulation Of The Allergen-Induced Asthma Phenotype, Ajay P Nayak, Deepak A. Deshpande, Phd, Sushrut D. Shah, Dominic R Villalba, Roslyn Yi, Nadan Wang, Raymond B. Penn

Division of Pulmonary and Critical Care Medicine Faculty Papers

The proton-sensing receptor, ovarian cancer G protein-coupled receptor (OGR1), has been shown to be expressed in airway smooth muscle (ASM) cells and is capable of promoting ASM contraction in response to decreased extracellular pH. OGR1 knockout (OGR1KO) mice are reported to be resistant to the asthma features induced by inhaled allergen. We recently described certain benzodiazepines as OGR1 activators capable of mediating both procontractile and prorelaxant signaling in ASM cells. Here we assess the effect of treatment with the benzodiazepines lorazepam or sulazepam on the asthma phenotype in wild-type (WT) and OGR1KO mice subjected to inhaled house dust mite (HDM; …

Adult Spiny Mice (Acomys) Exhibit Endogenous Cardiac Recovery In Response To Myocardial Infarction, Hsuan Peng, Kazuhiro Shindo, Renée R. Donahue, Erhe Gao, Brooke M. Ahern, Bryana M. Levitan, Himi Tripathi, David Powell, Ahmed Noor, Garrett A. Elmore, Jonathan Satin, Ashley W. Seifert, Ahmed K. Abdel-Latif

Physiology Faculty Publications

Complex tissue regeneration is extremely rare among adult mammals. An exception, however, is the superior tissue healing of multiple organs in spiny mice (Acomys). While Acomys species exhibit the remarkable ability to heal complex tissue with minimal scarring, little is known about their cardiac structure and response to cardiac injury. In this study, we first examined baseline Acomys cardiac anatomy and function in comparison with commonly used inbred and outbred laboratory Mus strains (C57BL6 and CFW). While our results demonstrated comparable cardiac anatomy and function between Acomys and Mus, Acomys exhibited a higher percentage of cardiomyocytes displaying …

Human Immunodeficiency Virus Type-1 (Hiv-1) Transcriptional Regulation, Latency And Therapy In The Central Nervous System, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Priya Tyagi, Alok Bhushan, Mudit Tyagi

College of Pharmacy Faculty Papers

The central nervous system (CNS) is highly compartmentalized and serves as a specific site of human immunodeficiency virus (HIV) infection. Therefore, an understanding of the cellular populations that are infected by HIV or that harbor latent HIV proviruses is imperative in the attempts to address cure strategies, taking into account that HIV infection and latency in the CNS may differ considerably from those in the periphery. HIV replication in the CNS is reported to persist despite prolonged combination antiretroviral therapy due to the inability of the current antiretroviral drugs to penetrate and cross the blood–brain barrier. Consequently, as a result …

Development Of A Novel Mir-3648-Related Gene Signature As A Prognostic Biomarker In Esophageal Adenocarcinoma, Donglei Zhang, Hang Yin, Thomas L. Bauer, Michael P. Rogers, Jeffrey B. Velotta, Clinton T. Morgan, Weijia Du, Ping Xu, Xiaozhe Qian

Surgery Faculty Publications

Background: Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature.

Methods: The gene expression data of 87 EA tumor samples and 67 normal tissue samples from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database were downloaded, respectively. Weighted gene co-expression network analysis (WGCNA), the CIBERSORT algorithm, and Cox regression …

Lack Of Interferon (Ifn) Regulatory Factor 8 Associated With Restricted Ifn-Γ Response Augmented Japanese Encephalitis Virus Replication In The Mouse Brain, Aarti Tripathi, Bhupendra Singh Rawat, Sankar Addya, Milan Surjit, Prafullakumar Tailor, Sudhanshu Vrati, Arup Banerjee

Kimmel Cancer Center Faculty Papers

Interferon regulatory factor 8 (IRF8), a myeloid lineage transcription factor, emerges as an essential regulator for microglial activation. However, the precise role of IRF8 during Japanese encephalitis virus (JEV) infection in the brain remains elusive. Here, we report that JEV infection enhances IRF8 expression in the infected mouse brain. Comparative transcriptional profiling of whole-brain RNA analysis and validation by quantitative reverse transcription-PCR (qRT-PCR) reveals an impaired interferon gamma (IFN-g) and related gene expression in Irf8 knockout (Irf82/2)-infected mice. Further, Ifng knockout (Ifng2/2) mice exhibit a reduced level of Irf8. Both Ifng2/2 and Irf82/2 mice exhibit significantly reduced levels of activated …

The Contribution Of Patient Reported Outcome Measures To Shared Decision-Making In Radiation Oncology At A Midwestern Comprehensive Cancer Center, Kellie Bodeker

Doctor of Philosophy in Translational Health Sciences Dissertations

Background. Chronic diseases, such as lung cancer, require a provider-patient relationship developed over time. This relationship fosters shared decision-making (SDM), a collaborative, dynamic information exchange and analysis between provider and patient regarding treatment and desired outcomes. Established benefits to SDM include an improved quality of life and decreased anxiety and depression. Despite established benefits, recent research suggests radiation oncologists are not engaging in SDM. A decision-aid tool utilizing patient reported outcome measures may increase SDM between radiation oncologists and patients with lung cancer. Patient-reported outcome measures, wherein the patient provides direct assessment of their health and quality of life, …

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Physiology Faculty Publications

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

RESULTS: Single-cell …

Student Research Mentorship Programme: A Novel Solution For Promoting Research In Medical School, Inaara Akbar, Russell S. Martins, Syeda Sadia Fatima

Medical College Documents

No abstract provided.

Facilitating Aging In Place And Community By Empowering Participation In Society: A Mixed Methods Study On The Co-Development Of A Theory Of Change With Suburban-Dwelling Older Adults, Emily Balog

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Baby boomers are steadily aging in America and represent an increased population in nearly every sector. In suburban communities today, older adults make up 51% of the population. Ninety-five percent of all older adults live in community settings and have expressed a desire to avoid costly institutionalization and to remain in their homes and communities, also called aging in place. Older adults in moderate income suburban communities are increasingly at a higher risk for institutionalization should their health or finances decline as the access to their wealth is within the home in which they dwell. This process …

Bridging The Knowledge-To-Action Gap: A Qualitative Description Of The Use Of Knowledge Translation In Entry-Level Doctor Of Occupational Therapy Capstones, Maria Martino

Doctor of Philosophy in Translational Health Sciences Dissertations

Although developments in the use of knowledge translation (KT) in occupational therapy practice and research are emerging, a gap in education remains. A recent revision of accrediting standards for doctor of occupational therapy (OTD) programs now specifies scholarly study that advances KT. However, little is understood of how this change in accreditation standards is being implemented, nor of its effect on OTD capstones. The purpose of this study was to describe how KT is reflected and can be promoted in entry-level OTD capstones. A descriptive qualitative design was used with semi-structured individual interviews of OTD faculty as well as content …

Development Of Vaccines And Antivirals Against Zika Virus, Aryamav Pattnaik

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV), an arbovirus, poses a major global human health concern because of its ability to cause congenital abnormalities and neurological diseases. While many candidate vaccines and antiviral drugs are in the developmental pipeline, none have been approved for use against ZIKV infection. This dissertation describes the characterization of one vaccine and two antiviral drug candidates against ZIKV infection. A bacterial ferritin-based nanoparticle vaccine, termed zDIII-F, is designed to display multiple copies of ZIKV E protein domain III on its surface. These stable nanoparticles are shown to induce robust antibody-mediated protection against lethal ZIKV infection in …

Hiv-1 Persistence In The Cns: Mechanisms Of Latency, Pathogenesis And An Update On Eradication Strategies., Shilpa Sonti, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Despite four decades of research into the human immunodeficiency virus (HIV-1), a successful strategy to eradicate the virus post-infection is lacking. The major reason for this is the persistence of the virus in certain anatomical reservoirs where it can become latent and remain quiescent for as long as the cellular reservoir is alive. The Central Nervous System (CNS), in particular, is an intriguing anatomical compartment that is tightly regulated by the blood-brain barrier. Targeting the CNS viral reservoir is a major challenge owing to the decreased permeability of drugs into the CNS and the cellular microenvironment that facilitates the compartmentalization …

Autophagy, Apoptosis, The Unfolded Protein Response, And Lung Function In Idiopathic Pulmonary Fibrosis, Pawan Sharma, Javad Alizadeh, Maya Juarez, Afshin Samali, Andrew J Halayko, Nicholas J Kenyon, Saeid Ghavami, Amir A Zeki

Center for Translational Medicine Faculty Papers

Autophagy, apoptosis, and the unfolded protein response (UPR) are fundamental biological processes essential for manifold cellular functions in health and disease. Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary disorder associated with aging that has limited therapies, reflecting our incomplete understanding. We conducted an observational study linking molecular markers of cell stress response pathways (UPR: BiP, XBP1; apoptosis: cleaved caspase-3; autophagy: LC3β) in lung tissues from IPF patients and correlated the expression of these protein markers to each subject's lung function measures. We hypothesized that changes in lung tissue expression of apoptosis, autophagy, and UPR markers correlate with …

Emerging Advances Of Nanotechnology In Drug And Vaccine Delivery Against Viral Associated Respiratory Infectious Diseases (Varid), Amir Seyfoori, Mahdieh Shokrollahi Barough, Pooneh Mokarram, Mazaher Ahmadi, Parvaneh Mehrbod, Alireza Sheidary, Tayyebeh Madrakian, Mohammad Kiumarsi, Tavia Walsh, Kielan D Mcalinden, Chandra C Ghosh, Pawan Sharma, Amir A Zeki, Saeid Ghavami, Mohsen Akbari

Center for Translational Medicine Faculty Papers

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and …

Covid-19 And The Impact On Rural And Black Church Congregants: Results Of The C-M-C Project, Lovoria B. Williams, Anita F. Fernander, Tofial Azam, Maria L. Gomez, Junghee Kang, Cassidy L. Moody, Hannah Bowman, Nancy E. Schoenberg

Clinical and Translational Science Faculty Publications

The COVID‐19 pandemic has had devastating effects on Black and rural populations with a mortality rate among Blacks three times that of Whites and both rural and Black populations experiencing limited access to COVID‐19 resources. The primary purpose of this study was to explore the health, financial, and psychological impact of COVID‐19 among rural White Appalachian and Black nonrural central Kentucky church congregants. Secondarily we sought to examine the association between sociodemographics and behaviors, attitudes, and beliefs regarding COVID‐19 and intent to vaccinate. We used a cross sectional survey design developed with the constructs of the Health Belief and Theory …

Circumcision As An Intervening Strategy Against Hiv Acquisition In The Male Genital Tract, Adhikarimayum Lakhikumar Sharma, Joseph Hokello, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Unsafe sex with HIV-infected individuals remains a major route for HIV transmission, and protective strategies, such as the distribution of free condoms and pre-or post-prophylaxis medication, have failed to control the spread of HIV, particularly in resource-limited settings and high HIV prevalence areas. An additional key strategy for HIV prevention is voluntary male circumcision (MC). International health organizations (e.g., the World Health Organization, UNAIDS) have recommended this strategy on a larger scale, however, there is a general lack of public understanding about how MC effectively protects against HIV infection. This review aims to discuss the acquisition of HIV through the …

An Update On The Hiv Dna Vaccine Strategy, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

In 2020, the global prevalence of human immunodeficiency virus (HIV) infection was estimated to be 38 million, and a total of 690,000 people died from acquired immunodeficiency syndrome (AIDS)–related complications. Notably, around 12.6 million people living with HIIV/AIDS did not have access to life-saving treatment. The advent of the highly active antiretroviral therapy (HAART) in the mid-1990s remarkably enhanced the life expectancy of people living with HIV/AIDS as a result of improved immune functions. However, HAART has several drawbacks, especially when it is not used properly, including a high risk for the development of drug resistance, as well as undesirable …

Diagnosis And Management Of Adolescents With Polycystic Ovary Syndrome In Primary Care: A Mixed Method Study To Explore Provider Behaviors And Barriers And Facilitators To Practice, J. Leocadia Conlon

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder in women of reproductive age, associated with complications of metabolic, reproductive, and psychological health. Adolescence is an optimal time for early identification of PCOS in order to mitigate long-term health risks. Pediatric primary care providers (pedPCPs) are the first-line for early identification and coordination of longterm comprehensive management. Limited information exists to describe how PCOS is addressed in primary care and if adolescent-specific guidelines are applied.

Objectives: Describe practice behaviors of pedPCPs in the diagnosis and management of PCOS, and identify barriers and facilitators to inform future interventions to optimize …

Combinatorial Use Of Both Epigenetic And Non-Epigenetic Mechanisms To Efficiently Reactivate Hiv Latency, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

The persistence of latent HIV provirus pools in different resting CD4+ cell subsets remains the greatest obstacle in the current efforts to treat and cure HIV infection. Recent efforts to purge out latently infected memory CD4+ T-cells using latency-reversing agents have failed in clinical trials. This review discusses the epigenetic and non-epigenetic mechanisms of HIV latency control, major limitations of the current approaches of using latency-reversing agents to reactivate HIV latency in resting CD4+ T-cells, and potential solutions to these limitations.

Assessing Pre-Exposure Prophylaxis Screening And Need Among Men Who Have Sex With Men And Transgender Persons Of Color: A Mixed Methods Case Study Of The Impact Dmv Demonstration Project, Brittany C. Wilbourn

Doctor of Philosophy in Translational Health Sciences Dissertations

Men who have sex with men (MSM) and transgender persons of color experience disproportionate, multi-level HIV risks. Pre-exposure prophylaxis (PrEP) is an evidence-based HIV prevention strategy; however, access to PrEP has been limited among this population. PrEP demonstration projects that target MSM and transgender persons and test the implementation of PrEP in real-world settings are underway. However, PrEP demonstration projects specific to MSM and transgender persons of color are limited and most demonstration projects do not consider the impact of the implementation process or organization contextual characteristics on PrEP outcomes. The Improve Measurable Participation and Access to Care and Treatment …

Translating Assessments Into Practice Using Principles Of Patient-Centered Measurement: An Exemplar Using The Coma Recovery Scale-Revised, Jennifer Ann Craft Weaver

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Disorders of consciousness (DoC) include different states (e.g., comatose, vegetative state/unresponsive wakefulness syndrome, minimally conscious state (MCS), and emerging minimally conscious state (eMCS)) following a severe brain injury. Yet, effective communication about treatment of patients with DoC is often inhibited because family caregivers and rehabilitation practitioners do not interpret recovery of consciousness in the same way (Epstein & Street, 2007; Weaver et al., 2018). Because a person may remain in a disordered state of consciousness for as long as two decades and receive multiple episodes of rehabilitation during that time, ensuring clear communication among family caregivers and rehabilitation practitioners …

Ap-1 And Nf-Κb Synergize To Transcriptionally Activate Latent Hiv Upon T-Cell Receptor Activation., Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Latent HIV-1 proviruses are capable of reactivating productive lytic infection, but the precise molecular mechanisms underlying emergence from latency are poorly understood. In this study, we determined the contribution of the transcription factors NF-κB, NFAT, and AP-1 in the reactivation of latent HIV following T-cell receptor (TCR) activation using Jurkat T-cell clones harboring single latent HIV proviruses. Our findings demonstrate that during reactivation from latency, NF-κB enhances HIV transcription while NFAT inhibits it by competing with NF-κB for overlapping binding sites on the HIV long terminal repeat (LTR). We have also demonstrated for the first time the molecular contribution of …

Chloroquine: Autophagy Inhibitor, Antimalarial, Bitter Taste Receptor Agonist In Fight Against Covid-19, A Reality Check?, Pawan Sharma, Kielan D. Mcalinden, Saeid Ghavami, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

The recent SARS-CoV-2 pandemic poses one of the greatest challenges to modern medicine. Therefore, identification of new therapeutic strategies seems essential either based on novel vaccines or drugs or simply repurposing existing drugs. Notably, due to their known safety profile, repurposing of existing drugs is the fastest and highly efficient approach to bring a therapeutic to a clinic for any new indication. One such drug that has been used extensively for decades is chloroquine (CQ, with its derivatives) either for malaria, lupus and rheumatoid arthritis. Accumulating body of evidence from experimental pharmacology suggests that CQ and related analogues also activate …

Timing Of Preoperative Surgical Antibiotic Prophylaxis Prior To One-To-Three Level Elective Lumbar Fusion, Akash Singh, Gregory Schroeder, Md, Jose Canseco, Md, Alexander Vaccaro, Md, Parthik Patel, Md, Ariana Reyes, Md

Phase 1

Introduction: Surgical site infections (SSIs) in patients who have undergone lumbar fusion surgery can be a devastating complication. The aim of this study was to examine the relationship between timing of preoperative antibiotic prophylaxis and adverse outcomes such as SSIs with subgroup analysis stratified by antibiotic type.

Methods: This retrospective cohort included patients having undergone a 1-3 level lumbar fusion who were allocated into 5 groups based on the time from antibiotic administration to incision (Group A = 0-15 min, Group B = 16-30 min, Group C = 31-45 min, Group D = 46 – 60 min, and Group …

Deep Supratentorial Extension Is Associated With Poor Clinical Outcomes After Glioblastoma Resection, Adam Barsouk, Michael P. Baldassari, Omaditya Khanna, Donald Ye, Erica Cunningham, Christopher Farrell, David Andrews, James Evans, Kevin Judy

Phase 1

Introduction: Glioblastoma (GBM) often extends to deep supratentorial locations, which limits the extent of maximal safe resection. Deep supratentorial extension (DSE) may be a clinically convenient prognostic indicator following GBM resection.

Methods: 582 GBM resections from 2012-2018 were retrospectively reviewed. DSE was defined as tumoral extension to the basal ganglia, thalamus, corpus callosum, internal capsule, hypothalamus, caudate, or putamen as identified on preoperative imaging.

Results: DSE was identified in 32.9% cases (192), while 52.5% (306) involved only superficial supratentorial locations (frontal, parietal, temporal and occipital lobes). Within the DSE cohort, the most commonly affected anatomical locations were the corpus …

Investigation Of The Reciprocal Relationship Between C7, Tsp1, And Tgf-Β Activation In Normal Fibroblasts, Alicia Kenyon, Andrew South, Phd

Phase 1

Introduction: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare skin blistering disorder due to a loss of function mutation in the collagen 7 (C7) gene. C7 activity loss upregulates thrombospondin-1 (TSP1), stimulating tissue growth factor-ß (TGF-ß), which promotes the development of cutaneous squamous cell carcinoma (cSCC) in RDEB patients. This C7-TSP1 interaction has not been described in normal fibroblasts; therefore, in this study, we tested the hypothesis that the level of intracellular C7 negatively correlates with TSP1 expression in normal fibroblasts.

Methods: In this basic research cell study, C7, TSP1, and pSMAD3 (phosphorylated SMAD3), a marker of TGF-ß activation, were …